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Cap analysis of gene expression reveals alternative promoter usage in a rat model of hypertension

S. Dahale, J. Ruiz-Orera, J. Silhavy, N. Hübner, S. van Heesch, M. Pravenec, SS. Atanur

. 2022 ; 5 (4) : . [pub] 20220107

Language English Country United States

Document type Journal Article

The role of alternative promoter usage in tissue-specific gene expression has been well established; however, its role in complex diseases is poorly understood. We performed cap analysis of gene expression (CAGE) sequencing from the left ventricle of a rat model of hypertension, the spontaneously hypertensive rat (SHR), and a normotensive strain, Brown Norway to understand the role of alternative promoter usage in complex disease. We identified 26,560 CAGE-defined transcription start sites in the rat left ventricle, including 1,970 novel cardiac transcription start sites. We identified 28 genes with alternative promoter usage between SHR and Brown Norway, which could lead to protein isoforms differing at the amino terminus between two strains and 475 promoter switching events altering the length of the 5' UTR. We found that the shift in Insr promoter usage was significantly associated with insulin levels and blood pressure within a panel of HXB/BXH recombinant inbred rat strains, suggesting that hyperinsulinemia due to insulin resistance might lead to hypertension in SHR. Our study provides a preliminary evidence of alternative promoter usage in complex diseases.

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$a The role of alternative promoter usage in tissue-specific gene expression has been well established; however, its role in complex diseases is poorly understood. We performed cap analysis of gene expression (CAGE) sequencing from the left ventricle of a rat model of hypertension, the spontaneously hypertensive rat (SHR), and a normotensive strain, Brown Norway to understand the role of alternative promoter usage in complex disease. We identified 26,560 CAGE-defined transcription start sites in the rat left ventricle, including 1,970 novel cardiac transcription start sites. We identified 28 genes with alternative promoter usage between SHR and Brown Norway, which could lead to protein isoforms differing at the amino terminus between two strains and 475 promoter switching events altering the length of the 5' UTR. We found that the shift in Insr promoter usage was significantly associated with insulin levels and blood pressure within a panel of HXB/BXH recombinant inbred rat strains, suggesting that hyperinsulinemia due to insulin resistance might lead to hypertension in SHR. Our study provides a preliminary evidence of alternative promoter usage in complex diseases.
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$a Ruiz-Orera, Jorge $u Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
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$a Silhavy, Jan $u Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
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$a Hübner, Norbert $u Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany $u Charité -Universitätsmedizin, Berlin, Germany $u DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
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$a van Heesch, Sebastiaan $u Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands $1 https://orcid.org/0000000195931980
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$a Pravenec, Michal $u Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
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